Regulation and Loss of Freedom are to Blame for Much of the Poor Strategy of Past Decades of Cancer Research

FDA bureaucrats see the role of their organization as that of a shield, removing as much risk as possible from medicine. Since it is impossible to remove all risk from any medicine, what this mission means in practice is that no individual bureaucrat ever wants to be held accountable for approving a therapy that later turns out to have unexpected consequences. It doesn't matter if those consequences occur in just a few individuals, while countless others benefit, or even if the medicine in question is actually responsible: the fickle press will rise up in arms; the lawyers will flock. Thus those FDA bureaucrats will always move in the direction of requiring ever greater proof from companies - the cost of commercial development has doubled for no reason other than this in the past decade. Along the way, they also remove the right to choose from patients, the ever-present authoritarian side to the goal of protection. No-one is permitted their own risk assessment, and no organization is permitted to help those patients willing to take educated risks.

There are more subtle, reaching, and harmful effects beyond the obvious ones noted above. The structure of regulation has changed the strategy of research and development for the worse. As the article here argues, it is the major contributing factor to the lack of progress in treatment of cancer over the last half century. The present regulatory environment incentivizes the sort of development programs that produce marginal, incremental results, that build on existing approaches. Bold new directions need not apply. The FDA makes the cost of development so high that only large organizations can follow through to the clinic, and large organizations are risk averse. Few leaders will be willing to take the sort of risks that lead to real, revolutionary progress.

Look at the history of chemotherapy research and you'll find a very different world than the one that characterizes cancer research today: fast bench-to-bedside drug development; courageous, even reckless researchers willing to experiment with deadly drugs on amenable patients; and centralized, interdisciplinary research efforts. Cancer research was much more like a war effort before the feds officially declared war on it. The whole cycle, from no chemotherapies at all to development, trial, and FDA approval for multiple chemotherapy drugs, took just six years, from 1948 to 1953. Modern developments, by contrast, can take decades to get to market.

Today, the National Cancer Institute and various other national agencies now largely fund research through grants. The proliferation of organizations receiving grants means cancer research is no longer primarily funded with specific treatments or cures (and accountability for those outcomes) as a goal. With their funding streams guaranteed regardless of the pace of progress, researchers have become increasingly risk-averse. As the complexity of the research ecosystem grew, so did the bureaucratic requirements. "16.8 percent of the total costs of an observational protocol are devoted to institutional review board interactions, with exchanges of more than 15,000 pages of material, but with minimal or no impact on human subject protection or on study procedures."

As R&D gets more expensive and compliance more onerous, only very large organizations - well-funded universities and giant pharmaceutical companies, say - can afford to field clinical trials. Even these are pressured to favor tried-and-true approaches that already have FDA approval and drugs where researchers can massage the data to just barely show an improvement over the placebo. (Since clinical trials are so expensive that organizations can only do a few, there's an incentive to choose drugs that are almost certain to pass with modest results - and not to select for drugs that could result in spectacular success or failure.) Of course, minimal improvement means effectively no lives saved.

The problem is clear: Despite tens of billions of dollars every year spent on research, progress in combating cancer has slowed to a snail's pace. So how can we start to reverse this frustrating trend? One option is regulatory reform, and much can be done on that front. Streamline the process for getting grant funding and institutional review board approval. Cut down on reporting requirements for clinical trials, and start programs to accelerate drug authorizations for the deadliest illnesses. One proposal is "free-to-choose medicine." Once drugs have passed Phase I trials demonstrating safety, doctors would be able to prescribe them while documenting the results in an open-access database. Patients would get access to drugs far earlier, and researchers would get preliminary data about efficacy long before clinical trials are completed.

More radically, it might be possible to repeal the 1962 Kefauver-Harris amendment to the Federal Food, Drug, and Cosmetic Act, a provision that requires drug developers to prove a medication's efficacy (rather than just its safety) before it can receive FDA approval. Since this more stringent authorization process was enacted, the average number of new drugs greenlighted per year has dropped by more than half, while the death rate from drug toxicity stayed constant. The additional regulation has produced stagnation, in other words, with no upside in terms of improved safety. Years ago, a Cato Institute study estimated the loss of life resulting from FDA-related drug delays from 1962 to 1985 in the hundreds of thousands. And this only included medications that were eventually approved, not the potentially beneficial drugs that were abandoned, rejected, or never developed, so it's probably a vast underestimate.



So give us an idea of whom to write to help this along. I think the average Senator / Congressman is just going to blow off anything from not important / not wealthy individuals.

Or whom to donate to.

Posted by: bmack500 at August 31st, 2018 7:27 AM

@bmack500: I can't say that I'm much in favor of changing the system from within. I think the most plausible of approaches to this problem is setting up some form of viable mass-market medical tourism, a more mature and organized industry than the current very ad-hoc and haphazard one, coupled to a generally accepted, cheaper, and more minimal set of safety regulations. History and other regulatory regions suggest that processes at a tenth or less of the cost of the FDA can still do the same job when it comes to filtering out harm.

Posted by: Reason at August 31st, 2018 9:20 AM

Those FDA bureaucrats will do what it takes to get a well-paying position in a large pharmaceutical company after they leave the FDA. The pharmaceutical industry spends more on lobbying than any other industry; it's hard to believe they are not getting some, if not most, of what they want.

Posted by: CD at August 31st, 2018 10:00 AM

I agree with Reason, better to the route of medical tourism. Not only for illness, but also for cosmetic surgery.

It would be nice to find a source to list the difference countries and companies that provide the varied services, cancer, stem cell, and CRISPR treatments along with the cosmetic ones with safety stats, and prices. T think this would be a HUGE service (this list) to the 1st world population who have not alternatives.

Posted by: Robert at August 31st, 2018 12:31 PM

Reason's response to bmack500 is spot on. CD points to the revolving door at FDA that has become worse at the FDA than the NRC/DOE. Almost complete regulatory capture. And don't think longevity/SENS is the only aspect of life affected by this institutional rot. Everyone should think about a "Strategic Relocation" bug out plan, like Marc Faber has executed.

Posted by: Tom Schaefer at August 31st, 2018 1:21 PM

It's not just loss of freedom due to bureaucrats covering themselves, it is also regulatory capture. Imagine if in the IT software industry for a startup to bring a new app or idea to market they had to sell a majority stake in their company to one of Google, Apple, Microsoft, Amazon, Facebook, Oracle, or Intel due to the cost of complying with regulation. High regulatory barriers help incumbents in a lot of industries. The big pharma companies have no real incentive to push for lighter regulation.

Posted by: Jim at August 31st, 2018 9:54 PM

It is a bit of a cop-out to say that we should give up on regulatory change and go for medical tourism. Perhaps if you really think that a wave of medical tourism will trigger the desired regulatory change and that it specifically is the most likely way to accomplish that, but I don't think that's what I just heard in the previous comments.

Simply enabling mass medical tourism is still going to leave lots of people untreated, and more importantly the big problem is that the huge regulatory barrier drives up costs for developing new therapies and thus slows the overall pace of research and innovation. Getting a 10x larger minority of the population an easier route to medical tourism does not really fix that problem. But switching to a system of putting treatments on the market once prove safe, and letting consumers and medical professionals make decisions of what to use based on the available data (and official recommendations from various orgs including possibly the FDA itself) *would* create the sea change that would unlock faster science and innovation.

We can argue about how unlikely that switch is, but it's clear that it's important, and I don't think medical tourism is likely to give the same magnitude of benefit to society.

Posted by: Karl Pfleger at September 1st, 2018 12:00 PM

@Karl Pfleger: Yes, medical tourism as a forcing function for regulatory change is the approach I advocate. See:

To treat tens of millions, therapies must be delivered to their locale. I do think that an optimal, much larger medical tourism market could treat an order of magnitude or two more people than the present market manages. But it is still the case that the primary goal of successful medical tourism is to change the regulatory status quo by providing a viable alternative to the FDA for biotech companies to become large enough and profitable enough to satisfy investors. At which point pressure will be applied to regulators and politicians, and change will result.

Posted by: Reason at September 1st, 2018 12:20 PM

So it will continue with corporatism i.e. corporations hand in glove with governments in the production of regulation that keeps the little guy out and, of course, with an infantalized population forever crying, 'Something must be done (about whatever)!' which is just what increasingly authoritarian states want to hear.

Posted by: Neal Asher at September 3rd, 2018 5:45 AM

NIH tells us best bet is to use natural substance transported in same way as cancers' only source of energy to live (which used to be made in our livers from that caloric source;which Otto Warburg won nobel prize for discovering was the only source of energy for cancer). But; alas will never be approved as a drug. Who will spend 1 Billion+$$$ to get a non-patentable substance approved as a "drug"? & cure the biggest $$$ making disease? Maybe ignorance is not bliss. If ignorance is of a harmless cure without negative "side" effects: shown to work by our N.I.H. ...

Posted by: Ray at September 12th, 2018 12:18 AM

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